Partnerships
Lecture Partnerships:
Pain for 2 hoursacute
Pain for 3 monthschronic
Neutrophils and yellowish sputumacute
Mononuclear cells (lymphocytes, macrophages)chronic
Rolling: E-selectin in context of adhesionSialyl Lewis x molecules on WBC
Pavementing: LFA-1 (Leukocyte function associated antigen on WBCs) w/ ICAM-1 &
VCAM (on endothelial cells)
Transmigration: CD31 or PECAM
Delayed separation of umbilical cordfucosyl transferase deficiency (selectin)? check
CGDNBT test for this condition
Partnerships reviewed by Gohara:
Defective organelles trafficking Chediak Higashi (albinism, fair eyelashes & eyebrows,
giant granules in neutrophils)
Defective NADPH Oxidase CGD (X-linked= gp91PHOX; autosomal recessive=
P47PHOX & P67PHOX)
C5achemotaxis
C3bopsonins
Immunoglobulinsopsonins
Prostaglandinscyclooxygenase pathway
Prostaglandinsvasodilation
NOvasodilation
PECAMtransmigration
Selectinrolling
ECAMPavementing
Mast cells histamine
Plateletsserotonin
MyeloperoxidaseHOCl
Arachidonic acid metabolitescyclooxygenase and lipoxygenase
Vasoactive aminesserotonin and histamine
Leukocytes stickingintegrin
Delayed separation of umbilical cordselectin deficiency/defects
Kininogen + Kallikreins kinins
Activated factor XII converts prekallikreins to kallikreins—cleaveHMW Kininogin to
Bradykinin
*Kinins are inactivated in the lung by ACE
Kallikreins & PAF cleave plasminogen to plasmin cleaves C3 and activates factor XII
(Cycle)
Erythema nodosumsarcoidosis, Type IV hypersensitivity, unknown etiology
Morphologic pattern of acute inflammation:
Serous (effusion and blisters)viral infections and burns
Fibrinous (proteinaceous material accumulating as a result of inflammation)Uremic
pericarditis or pleura
Diseases of Blood Vessels:
Which of the following cells is responsible for initial lesion of atherosclerosis=
endothelial cells
Atherosclerosis= disease of intima (single layer of endothelial cells and minimal CT)
Disease of media= Monckeberg’s sclerosis
Progression of atherosclerosis= smooth muscle cells
Hyalinization= (see a story about someone with high BP for long time and controlled
with medications); appearance of blood vessels with benign hypertension
Onion skinning (causes major medical emergencies)= malignant hypertension
(hyperplastic arteriolosclerosis)
Pts with diabetes= more prone to developing atherosclerosis bc always have high
cholesterol and high triglycerides
*very important* high sensitivity to C reactive protein= risk assessment test; if pt has
high sensitivity elevated C reactive protein, at higher risk for developing MIs and strokes
Hyalinization of blood vessels occur in benign hypertension and diabetes
Review of Diseases of Blood Vessels:
Mutation of LDL receptor= Hyperlipidemia Type IIa (Familial Hypercholesterolemia)
High sensitivity C reactive protein= risk factor for ischemic heart disease and stroke
Lipoprotein-a (an altered LDL) when in large quantities= risk factor for atherosclerosis
Familial Homocysteinemia= premature ischemic heart disease
Calification in the media= Monckeberg’s Atherosclerosis
What type of patient, what type of presentation, what type of complications?
What does it mean to you when you see Hyperplastic Arteriosclerosis? = malignant
hypertension= onion skinning
Vignette: a person with this lesion (malignant hypertension)
How are they going to present? Onion skinning in arterioles, could be in
microangiopathic hemolytic anemia; schistocytes on peripheral blood smear, diastolic P
>120 mmHg (maybe 200/130)
What complication?
An older lady dies at home. Long history of hypertension and diabetes well-controlled
by medication. Do an autopsy. What do you expect to see at autopsy in arterioles?
Will see HYALINIZATION bc this woman most likely had benign hypertension. Both
benign hypertension and diabetes cause hyalinization of the arterioles.
**Smooth muscles prolif, occlude, and form fibrous cap.= point of no return once get this
cap
Thickened intima (genetic)= response to vascular injury
We are going to choose which scenario it will be associated with:
Scenario 1: a 32 year old man and he comes in to the derm clinic bc he has a lesion on his
penis, it’s kind of ulcerated but not painful. He doesn’t use protection, and this lesion has
been there for about 5 days.
Scenario 2: the same man, but now about 2 months later, and he doesn’t have that
ulcerated lesion anymore but some rash on his palms, and he just doesn’t feel right.
Scenario 3: that man about 10-15 years later, comes in with dyspnea, dysphagia, and
heart failure, and some neurologic manifestations (sensory loss) this one associated
with thoracic aneurysms
Loss of elasticity in media due to ischemia caused by inflamm of vasovasorum causes
intima to wrinkle/fold.
Treebark appearance of blood vessel intimal surface=Syphilis
Ascending aorta aneurysm= Syphilis
Medial necrosis & dissection= Marfan’s Syndrome
Ripping chest pain/tearing chest pain radiating to the back and hypertension= Aortic
Dissection
Anything in which pain radiating to the backthink of something that perforated
e.g. abdominal pain, started suddenly, 75 yo male with hypertension and
atherosclerosisruptured aortic aneurysm
ruptured bowel or vesselpain radiates to the back
acute pancreatitis also radiates pain to the back
Inflammatory Diseases of Blood Vessels:
pANCAAntimyeloperoxidase (myeloperoxidase is in granules that generate free
radicals) Churg Strauss, Microscopic polyangitis, Polyarteritis Nodosa (very small # of
pts)
cANCAAnti Proteinase 3 (proteinase 3 present in azurophilic granules)Wegener
granulomatosis
stiffness and pain in shoulderstemporal arteritis (inflammation of small and medium
sized arteries, esp temporal arteries) Polymyalgia rheumatica
treebarksyphilis
medial necrosis Marfan’s
cANCA- Wegener
pANCA- Churg Strauss, Microscopic Polyangitis, and small % PAN
polymyalgia rheumaticatemporal arteritis
beefy tongue Kawasaki
cold arm Takayasu
smokingBuerger’s (or Thromboangiitis Obliterans)
renal involvement Wegener, Microscopic Polyangitis, and PAN
Partnerships reviewed:
Tree barksyphilis
Eosinophilia Churg-Strauss (is the main partner), the behind the scene partner is PAN
Asthma Churg-Strauss
cANCA (antigen= proteinase 3)Wegener
Polymyalgia rheumatica temporal arteritis
Branches of aortic archTakayasu (young females get)
Severe leg pain and smokingBuerger’s
Non-responsive high fever 5 days in a childKawasaki
pANCAChurch Strauss and small percentage of PAN
Hep BPAN
SinusitisWegener (sinusitis, glomerulitis, pneumonitis)
Ripping chest pain radiating to the backdissecting aneurysm of the aorta
2 possible causes:
Marfan
Severe hypertension
If Marfan medial necrosis (cherish and frame it)
What else could he have? Mitral valve prolapse
45 yr old pat with severe epigastric pain and hematuria and CBC eosinophiliaPAN
(does not affect the lungs), affects GI, skin, and kidneys
70 year old man presents with large thoracic aortic aneurysm. What should we ask him?
Syphilis! (always always always ask)
Diseases of Endocardium:
Clinical vignette:
8 yo boy brought in by his mother because of a swollen, red, tender left knee and right
wrists. He also had a reddish rash on his chest (erythema marginatum). He has not been
feeling well since he had a sore throat a couple weeks ago.
PE: temp 101 degrees F, pulse 100/minute, friction rub heard on chest auscultation
Dx: Rheumatic Fever
Jones Criteria:
Major: carditis, polyarthritis (migratory), sydenham’s chorea, E. marginatum,
subcutaneous nodules
Minor: fever, arthralgia, increased ESR, increased PR interval on EKG
need 2 major or 1 major + 2 minor
Erythema marginatumpink rash, clear center with red serpingenous margins on trunk
(never on face), transient and migratory nonpruritic, nonindurated, blanches on pressure
Aschoff bodies (nodules), anitschow cells (caterpillar nucleus cell, macrophage according
to Robbins), aschoff cells (giant cells with owl-eye nucleus)Rheumatic Fever
“bread and butter appearance” pericarditisFibrinous pericarditispost MI, Dressler
Syndrome, Rheumatic Fever/Pericarditis
Aschoff bodiesmyocarditis
Verrucous endocarditis at line of closure of valves on side of blood flowRheumatic
Fever
10 yo boy who arrived from Cambodia two months ago, presents to ER w/ fever 103F,
chills, petichiaie under his nails
PE tender nodules in elbows, hemorrhagic spot on retina
Dx: subacute endocarditis, probably had RF in the past
Subacute endocarditisoccurs on abnormal valves, less virulent microorganisms such as
streptococcus viridans, indolent course (wks to mos), full recovery in most cases with tx
Acute endocarditisoccurs on normal valves, highly virulent microorgs such as staph
aureus, destructive and rapidly progressive, death within days to weeks, IV drug users
Petechiae, splinter hemorrhages (nails), Janeway lesions (palms and soles: painless
hemorrhagic lesions), Subcutaneous (Osler nodes: hemorrhagic painful), Roth spots
(hemorrhage on retina)
Septic infarcts and abscesses, glomerulonephritis (immune complex
deposition)complications of endocarditis
Marantic Endocarditissterile endocarditis associated with malignancies, Troussea sign
(mucinous adenocarcinoma of the pancreas)
SLE endocarditis, small vegetations on both sides of valves, hematoxylin bodies (look
like naked nuclei)Libman-Sacks Disease
Thick plaques in right side of heart on tricuspid valve, acid mucopolysaccharides with
matrix, increased serum levels of serotoninCarcinoid Heart Disease
Mid-systolic clickmitral valve prolapse, sometimes associated with Marfan’s
Syndrome
Elderly person with angina, CHF, and syncopecalcific aortic stenosis (commonly
bicuspid valves, especially if younger person such as in 50s)
pulsus paradoxicus, muffled heart soundsConstrictive pericarditis
painful, modified smooth muscle cell tumors, distal digits under nails, arise from glomus
body (A-V shunt in dermis)glomus tumors
polyvinyl chloridehemangiosarcoma of liver
cardiac myxomas (CT tumor with mucus), skin myxomas, hyperpigmentation,
endocrinopathies, autosomal dominant syndromeCarney Syndrome
rhabdomyoma (skeletal muscle tumor of myocardium)tuberous sclerosis
adriomycindilated cardiomyopathy
radiation therapyscarring, fibrosisadhesive pericarditis
18 yo man to ER with fever 104F, tachycardia 5 days after tooth extraction
PE: new systolic murmur, hemorrhagic spot on retina
IE: Infectious endocarditis
Do Blood cultures
Congestive Heart Failure:
OrthopneaLeft-sided heart failure
Congestion, pulmonary edemamacrophages come in to clean up hemorrhaging
“heart failure cells” (have hemosiderin in them, Fe from broken down blood cells)
Right heart failureliver congestionnecrosis of liver cells around central
veinincreased LDH5
B-type Natriuretic Peptide (BNP)regulates BP and from the heartelevated in CHF
Alcohol, peripartum, genetic, myocarditisdilated cardiomyopathy (heavy flabby heart,
thin walls)
Alcohol dilated cardiomyopathydirect toxicity or thiamine deficiency
Increased levels of an antiangiogenic cleavage product of prolactinperipartum dilated
cardiomyopathy
Mutation of a dystrophin gene (main one) or alpha cardiac actin in terms of
heartgenetic dilated cardiomyopathy (“put on night stands”)
Adriomycin toxicity (Boo! I had this!)myocarditis
Mutations in myosin binding protein, beta myosin heavy chain, troponin
THypertrophic cardiomyopathyhypertrophy in septum obstructing outflow through
aortic valveoften young athletes who collapse and die
Hypertrophy of heart and on microscopy, sarcomeres not arranged in normal layers
(disorganized appearance)Hypertrophic cardiomyopathy
Cor pulmonale (long-standing lung disease)isolated right ventricle hypertrophy
Glomerular Diseases:
Fixed Tissue AntigensGood Pasture Syndrome anti GBM (Glomerular Basement
Membrane) Nephritis
Immune Complex Nephritis (immune complex circulating and depositing in basement
membrane, activating complement, PMNs, lysosomal enzymes cause tissue damage)
post-streptococcal glomerulonephritis + low serum complement
Low serum C3 (alternative pathway-mediated) membranoproliferative
glomerulonephritis
Nephrotic Syndrome thickening of basement membrane capillaries*, proteinuria,
hypoproteinemia, edema of legs, hyperlipidemia, lipiduria
Nephritic Syndrome *hematuria, *RBC casts (RBCs that have taken the shape of renal
tubules from sitting there for awhile), *azotemia (increase in nitrogenous waste products
in the serum) proliferation of mesangial cells* and necrosis, mild proteinuria,
hypertension, oliguria
Hematuria Syndromevariable changes in the glomeruli
Chronic Renal FailureHyalinization or sclerosis (scars) of glomeruli
Collagen Type IV of basement membrane completely impermeable to albumin
Nephrintransmembrane glycoprotein in the slit diaphragm that forms disulfide bridges
between adjacent podocytes
Nephrin and podocincrucial role in maintaining selective permeability of glomerular
filtration barrier
Mutations of nephrin or podocinabnormal leakage of plasma proteinsFamilial
nephrotic syndrome
Resident glomerular mesangial cells can initiate an inflammatory response in the
glomerulus
5 year old was brought to the emergency room because the mother had noted dark urine
(looks like Coca Cola or Tea). The child had a sore throat 10 days earlier.
Physical Exam BP:120/80 (high for age)
Urinalysis: RBCs, RBC casts, 1+ protein (not significant), CBC nl, ESR elevated, BUN
elevated, Creatinine elevated (these last two are collectively referred to as azotemia)
Dx: Post-Streptococcal glomerulonephritis (Immune Glomerulonephritisimmune
complexes in membrane)
Clinical picture: hematuria, hypertension, azotemia
Lab Findings: ASO titer increased, complement (CH50, C3 & C4) low bc of classical
pathway activation by immune complexes, RBCs + RBC casts in urine, elevated BUN,
elevated Creatinine
Morphology: Mesangial Cell Proliferation (*characteristic of nephritic syndrome)
IF: Lumpy Bumpy (Coarse Granular) peripheral deposits of IgG and C3 on BM
EM: Subepithelial electron dense humps
Post strep glomerulonephritislow complement, increased ASO, Humps on EM
(subepithelial), mesangial proliferation
A 5yo boy comes to the clinic with a hx of tea color urine for 3d and a past hx of a severe
skin rash with pustules 3 wks ago
Infection: impetigo (caused by strep)
What would you expect to see in his urine? RBCs and RBC casts
What would you see on a renal biopsy?
LM: mesangial cell proliferation
IF: lumpy bumpy IgG and C3
EM: subepithelial humps
A 35 yo male went to his physician for an annual physical. He was found to have
microscopic hematuria.
CBC nl and CHEM20 nl
DD: Hematuria Syndrome as a result of IgA nephropathy (also known as Berger’s
Disease)
LM: variable
IF: diffuse mesangial IgA
Tx: steroids
Prognosis: benign in children; can progress to renal failure or hypertension in adults;
recurrence in allografts
IgA Nephropathydiffuse mesangial IgA and recurrence in renal allografts (suggests a
problem in immune system rather than the kidney~Wikipedia)
A 12 year old girl presents with a palpable red rash on her buttocks, arthralgia, abdominal
pain, and hematuria.
UA: RBCs and RBC casts; BUN, creatinine, and serum IgA increased (nephritic
syndrome)proliferation of mesangial cells
Dx: Henoch-Schonlein purpura*GI, skin, & kidney involvement; *IgA deposits in skin
and kidney; *nl bleeding time; preceding illness usually an upper respiratory tract
infection
A 25 yo male presents with profuse hemoptysis following a flu-like illness a week prior
Physical examination: pale, tired young man
Urinalysis: many RBCs, many RBC casts
CBC: Hemoglobin 11
DDx: Good Pasture’s, Wegener’s
hemoptysis and hematuriaGood Pasture’s and Wegener’s
Good Pasture’s Syndrome*hematuria, *hemoptysis, *anti-GM (glomerular basement
membrane) antibodies against *alpha 3 chain of Collagen Type IV, URI preceding
symptoms
LM: necrosis, crescents
IF: linear peripheral Ig deposits** along glomerular BM and alveolar septa
Crescentic glomerulonephritisleakage of fibrin in Bowman’s space, proliferation of
parietal cells (lining Bowman’s capsule)crescent= fibrin and parietal cells lining
bowman’s capsule rapidly progressing glomerulonephritis (according to website with
pic below, occurs in post-strep, lupus, Good Pasture, vasculitis, and idiopathic)
(Crescents are defined as the presence of 2 or more layers of cells in the Bowman space. The
presence of crescents in glomeruli is a marker of severe injury. Cells and mediators from the
interstitium enter the Bowman space with disruption of the Bowman capsule, which leads to
development of crescents.
The major participants in crescent formation are coagulation proteins, macrophages, T cells,
fibroblasts, and parietal epithelial cells. Activated macrophages contribute to the crescents by
proliferating and releasing procoagulant tissue factor, interleukin-1 (IL-1) and tumor necrosis factor
(TNF). T cells are not prominent components, but they play an important role in glomerular injury by
antigen recognition and macrophage recruitment.
http://emedicine.medscape.com/article/239504-overview)
http://www.pathologyatlas.ro/rapidly-progressive-crescentic-glomerulonephritis.php
A 45 yo F with a three month history of epistaxis presents with cough and hematuria.
Wegener GranulomatosiscANCA positive, clinical triad: sinusitis, pneumonitis
(cough, hemoptysis can be present), glomerulonephritis (hematuria), see crescents under
light microscoperapidly progressive glomerulonephritis (progresses to renal failure
within weeks or months)
A 50 yo Executive presents with recurrent abdominal pain and a skin rash. He has had a
low grade fever for three months. BP 140/90, Temp 100 F (oral), UA RBCs, RBC casts,
1+ protein, CHEM 20: BUN50, Creatinine 3azotemia, CBC Eosinophilia, other tests:
Hep B positive in 30% of cases, pANCA positive in small % of cases
Dx is Polyarteritis Nodosa (PAN); Polyarteritis= multiple arteries inflamed, Nodosa=
aneurismal dilatation in segmental fashion
Polyarteritis Nodosa (PAN)*Hepatitis B (30%), *segmental arteritis, *NO lung
involvement, *GI, *skin, *kidney, musculoskeletal, CNS, small % have pANCA
Other info: Male:Female= 15:1, mostly occurs in 5th and 6th decades; pathogenesis is
chronic immune complex with hypersensitivity (no one preceding illness to trigger)
An IV drug user presents with a skin rash & hematuria
DD? Hep BPAN
CBCeosinophilia
UAnephriticRBCs and RBC casts
Hemolytic Uremic Syndrome (HUS) Vignette
A 3 yo boy presents to the ER with hematuria and bloody diarrhea for 2 days following a
birthday party where he ate a grilled hamburger.
CBC: Hb7, BUN and creatinine high (azotemia), low platelets, schistocytes on peripheral
blood smear (microangiopathic anemia)
Pathogenesis: intravascular coagulationdecreased plts, increased fibrin split products
CP: oliguria, renal failure, hemolytic anemia, E. Coli 0157:H7 toxins in stool
HUS identical to TTP except no neurological manifestations
HUSundercooked hamburger, E.coli 0157:H7, hematuria, renal failure,
microangiopathic hemolytic anemia
Microangiopathic hemolytic anemias (Schistocytes)HUS, Scleroderma, TTP,
Vasculitis, DIC, Malignancies; low platelets; normal platelets
Systemic Lupus Erythromatosis affects skin, heart, joints, kidney (ultimately kills
them), lab findings: ANA increased (anti-smith antibody: the smith antigen is a
complex of RNA and proteins that form small ribonucleic proteins which ultimately
come together with others to form spliceosomes, which cuts out introns of pre-mRNA to
mRNA), anti DNA increased, complement decreased all of them bc classical pathway
(CH50 low, C3 and C4 low), hematuria, proteinuria, casts, nephrotic syndrome (First Aid
says nephritic or nephrotic)
IF: IgG + C’ in mesangium and tubules “full house fluorescence”*
EM: subendothelial deposits*
Vignette: Scleroderma AKA Progressive Systemic Sclerosis
45 yo F with hypertension* and pulmonary fibrosis* and Raynaud’s phenomenon* for 5
years presents with renal failure*.
ANA 1:20,000 speckled anti SCL70 positive*
Most also have dysphagia*
She has thin leathery skin on her hands and face due to scars
21 yo man with gross hematuria, BUN nl, creatinine nl, BP nl,
What will you see on a renal biopsy? Diffuse mesangial IgA
Dx: pure hematuria Hematuria Syndrome (IgA nephropathy) (listed under Nephritic
Syndrome in First Aid, but not in Dr. Gohara’s notes)
10 yo boy with a rash on face, arthralgia, and renal failure
UA: RBCs and casts
BUN is elevated
Creatinine is elevated
What would you like to ask? Infections? NO, rash palpable? NO, abdominal pain? NO
What tests? ANA 1:2000 speckled, anti dsDNA++, anti Smith +++
Dx: Lupus
What are you going to see in a renal biopsy? Subendothelial deposits
31 yo man IV drug user presents with severe epigastric pain and a rash on his chest. Also
has hematuria.
Questions to ask: Hep B? YES
Dx: PAN
CBC: eosinophilia
Nephrotic Syndromes:
Primary- Lipoid Nephrosis (Minimal Change Disease), Focal Glomerulosclerosis,
Membranous Glomerulonephritis, Membranoproliferative Glomerulonephritis
Secondary- Diabetes, Amyloidosis
*Clinical: edema (especially in ankles due to decreased oncotic pressure), 4+ proteinuria
(>3 gm ptn lost in 24 hours), hypoproteinemia due to loss of proteins in the urine,
hyperlipidemia
*Proteinuria due to leaky capillary basement membrane leading to frothy urine
*Hyperlipidemia (unknown cause) leads to increased risk of atherosclerosis and *oval fat
bodies* in the urine (tubular cells filled up with lipid)
--USMLE World Qbank also said that Nephrotic Syndrome presents with
thrombi/increased risk of clotting due to loss of antithrombin in the urine.
2 vignettes for Lipoid Nephrosis (AKA Minimal Change Disease):
1) a 2 yo boy with recurrent nephrotic syndrome is found to have selective proteinuria*
(mostly albumin in urine)—80% of primary nephrotic syndrome in children is this.
2) a 40 yo lady with a hx of left-sided neck pain for 3 months with accompanying
lymphadenopathy*, and the pain gets worse when she drinks her glass of wine* with her
dinner. 10 days ago she noted swelling of her feet* and frothy urine*. *Hodgkin’s
Lymphoma *Nephrotic Syndrome—30% of primary nephrotic syndrome in adults is this
Pathogenesis: T cell factors damage podocytes, proteins leak out of foot processes and
they then become sticky and fuse together “podocyte foot processes effacement”*
Nothing on LM, EF. Just EM: fusion of foot processes*
Usually no preceding illness
Good response to steroids*
Focal Segmental Glomerulosclerosis (FSGS) hematuria and NONselective
proteinuria*, NO response to steroids*, 60% nephrotic syndrome, 30% azotemia (*mixed
nephrotic and nephritic syndromes*), 25% hypertension, recurrence in renal allograft*
Morphology:
LM: juxtamedullary glomeruli (corticomedullary) focal necrosis which spreads
superficially as the disease progresses (segments of glomeruli have scarring and focal
means some glomeruli will have scarring and some will not)
Types:
-C1q—very poor prognosis
-collapsing with HIV*partnership
-collapse of the entire glomerulus—very large Bowman’s space as a result
-podocyte hyperplasia associated with HIV or drugs
-poor prognosis
A 15 year old with a history of malignant lymphoma (Non-Hodgkin’s) presents with
nephrotic syndrome. All tests negative except urinalysis: 4+ protein
Dx: Membranous Glomerulonephritispartners HAVE TO KNOW: hepatitis B, tumor
(Non-Hodgkin’s), poison ivy, immune complex disease (e.g. lupus), syphilis, malaria,
renal vein thrombosis
Pathogenesis: chronic immune complex, so slow progessing, and thus complement level
is nl
LM: thick basement membrane
IF: fine granular subendothelial deposits (in BM) with Ig and C3
Stages (MUST KNOW)
1- epimembranous deposits sitting at periphery
2- intramembranous deposits and basement membrane spikes
3- intramembranous depisits totally surrounded by BM
4- radiolucent areas where deposits used to be
NO response to steroids
Hepatitis B
2 partners:
1)PAN—nephritic syndrome
2) Membranous Glomerulonephritis—nephrotic syndrome
Membranoproliferative nephritis:
Type I= Mesangio Capillary Disease
Type II= Dense Deposit Disease
Vignette for Mesangio Capillary Disease:
A 5 yo F with nephrotic syndrome, hypertension, and hematuria for the last 6 mos. She
has a hx of hearing problems. Her uncle died at the age of 22 with chronic renal failure.
CBC: Hemoglobin 10, indices normal
Chem 20: BUN 20, Creatinine 3impaired renal function
UA: 2+ blood, RBC casts (these two are nephritic), 4+ protein (nephrotic)
LM: lobular pattern proliferation, increased mesangial matrix, thickening of BM
Females>males, immune complex disease so low C3 and C4 due to Classical
Complement Pathway, thick basement membrane (nephrotic) and proliferation of
mesangial cells (nephritic) which cause *split basement membrane
*recurs in renal graft
IGA nephropathy
Focal Segmental Glomerulonephropathy
Membranoproliferative Glomerulonephritis Type I (Mesangio Capillary Disease)
recurrence in renal allografts
Dense Deposit Disease
Mean age usually 16
Chronic glomerulonephritis
Post infection such as strep or pneumonia
Pathogenesis: alternative complement pathway*decreased C3*
LM: same as mesangio capillary disease
IF: discontinuous linear deposit of C3 peripherally…with antibody to C3 according to her
picture on p.327…though this she did not explain in class or on her slides, also says
“most patients have detectable circulating C3 nephritic factor, an IgG autoantibody”
EM: ribbon-like deposits in lamina densa
Systemic Diseases:
Diabetes and Amyloidosis
Diabetic Nodular Glomerulosclerosis (AKA Kimmelstiel-Wilson Disease)*nodular
sclerosis (thick capillary loops with nodules), *hyalinization of afferent and efferent
arteriolesthickened BMs of capillaries occurs in all organs, particularly in uncontrolled
diabetes, leading to MI, gangrene, neuropathy, skin lesions, retinal lesions, and renal
disease as a result of compromised blood flow
Amyloidosis:
Familial: 3rd decade
Primary: 6th decade
Secondary: 4th decadeassociated with multiple myeloma (back pain-lytic bone lesions,
frothy urine (proteinuria), constipation (due to hypercalcemia caused by lytic bone
lesions))
LM: nodular lesion, apple-green birefringence with congo red stain (little yellowgreenish fibers)
EM: non-branching fibrils in BM, mesangium and vessel walls
Slow downhill course to renal failure, NO response to steroids
Nodular lesions: amyloidosis, diabetes, and light chain nephropathy (see later notes)
Low C3: post strep, membranoproliferative type I and II, lupus
Low C3 & C4: post strep, membranoproliferative type I, and lupus
Review of last lecture for glom diseases:
45 yo archeologist who returns from a trip to Africa 3 weeks later he comes to the
emergency room with fever, chills, and headache. These episodes of fever chills and
headaches have recurred 3 times in 4 weeks. 2 weeks later he has frothy urine.
What is his systemic illness and what is his renal problem? Malaria, Membranous
Glomerulonephritis (nephrotic syndrome)
14 yo boy who comes in with nephrotic syndrome. He is known to have hearing
problems.
So what do you think his renal disease is? Mesangio Capillary Disease AKA
Membranoproliferative Type I
What do you think we would see on electron microscopy? Mesangialization, migration of
mesangial cell in BM and this splits it, giving a tram track appearance
25 yo HIV positive male presents with nephrotic syndrome.
What is his renal disease? Collapsing Focal Segmental Glomerulosclerosis
If see spikes in context of glomerular disease: basement membrane protrusions in stage 2
of membranous glomerulonephritis
Hepatitis C (FA also says HepB), what kidney disease is associated?
Membranoproliferative Type I
Which disease sometimes is familial? IgA Nephropathy, Membranoproliferative Type I,
and amyloidosis
Mesangialization on EMmembranoproliferative Type I
Lung fibrosis and renal diseasescleroderma
Apple-green birefringence in the glomerulusamyloidosis
Kimmelstiel-Wilson lesionsDiabetic Nodular Glomerulonephritis
Hyalinized afferent and efferent arteriolesdiabetes
Selective proteinuria Minimal Change Disease (Lipoid Nephrosis)
Nephrotic/Nephriticboth have blood and protein in urine: 1) Focal Segmental
Glomerular Sclerosis 2)Membranoproliferative Glomerulonephritis
Recurs in renal allograft: 1)IgA Nephropathy 2)Focal Segmental Glomerulosclerosis
3)Membranoproliferative Type I
Palpable rashHS purpura
IgA deposits in the skinHS purpura
Ribbon-like deposits in lamina densa on electron microscopymembranoproliferative
disease Type II (Dense Deposit Disease)
Alternative Complement Pathway Activation membranoprolif Type II
Non-Hodgkin’s lymphomaMembranous Glomerulonephritis
Subendothelial depositslupus
Urinary Tract Infections, Renal Hypertension, Tubular Necrosis (+ some other stuff
Dr. Gohara threw in from previous lectures)
Acute pyelonephritisWBC casts
Major complication: papillary necrosis
CP: sterile pyuria and severe flank pain radiating to the groin
4 causes of papillary necrosis:
1) acute pyelonephritischronic pyelonephritis and inflammation
2) Diabetes
3) Sickle cell anemia
4) Analgesic abuse
Last 3 mech is ischemia
Older male w/large prostateincreased risk of urinary tract infections
Pulmonary endotheliumACE
Fibrinoid necrosis of blood vessels malignant hypertension
Hyalinizationbenign hypertension
Sickle Cell Disease papillary necrosis (ischemia)
Eosinophiluriaantibiotic useacute interstitial nephritis
Papillary necrosis sickle cell disease, diabetes, acute pyelonephritis with obstruction,
analgesic nephritis (chronic interstitial nephritis)
Tubulorrhexis Ischemic tubular necrosis (can be caused by blood transfusion
mismatch—get hemolysis of RBCs and resulting ischemia)
Oxalate crystals in urine ethylene glycol (antifreeze)
Segmental tubular damage ischemic tubular necrosis
Sterile pyuriapapillary necrosis
Onion skinning chronic malignant hypertension
Urea splitting organismproteus (stones)
Staghorn stone stone obstructing pelvis of the kidney (large)
Pylonephrosis obstruction and then superimposed infection (kidney is a pocket of pus)
Hepatitis C membranoproliferative Type I*
Nodular lesions Diabetes, amyloid, light chain disease *
Non-branching fibers on EM amyloid*
Berger disease(another name is) IgA nephropathy*
Light chain nephropathy multiple myeloma
17 yo male presents to the ER with hematuria, headache, and blurred vision, BP 205/130
Dx malignant hypertension
Renal morphologyfibrinoid necrosis of blood vessels
55 year old lady with RA for 20 years with severe renal colic and sterile pyuria
Dx: papillary necrosis
What caused it: analgesics for her RA
Berry aneurysmadult polycystic kidney disease
Lamellation of lamina densaalport
Radially arranged cystsinfantile type polycystic disease
Cysts in the liveradult polycystic disease
45 yo male presents with hypertension, hematuria, and bilateral flank discomfort. His dad
is 65 and has been on renal transplant list for 7 yearsadult polycystic disease
A 6 yo girl has hearing problems and hematuria
Dx: Alport*
Pathogenesis—alpha 3 and alpha 4 chain of collagen type IV is mutated*
Differentiate from Membranoprolif type I is mixed (both nephrotic (protein) and
nephritic (blood))—she just has blood
Congenital Familial Renal Diseases (reviewing notes)
Infantile Polycystic Disease (Potter Type I)radially arranged cysts extending through
cortex and medulla in the interstitium, incompatible with life bc no room for nl tissue,
autosomal recessive*, oligohydramnios (little amniotic fluid) during pregnancy*,
Mutation in PKHD1 gene* that codes for a membrane-receptive protein called fibrocystin
(Fibrocystin is a large, receptor-like protein that is thought to be involved in the
tubulogenesis and/or maintenance of duct-lumen architecture of epithelium~Wikipedia)
Dysplastic Kidney (Potter Type II)sporadic and usually unilateral (if bilateral=
incompatible with life), usually associated with CNS abnormalities and esophageal
atresia, lots of cysts and remnants of mesenchymal tissue especially cartilage
Adult Polycystic Kidney (Potter Type III)abnormality of interstitial regions and
multiple small cysts initially and manifest in late 30s early 40s as cysts become larger, fill
with fluid, and compress on surrounding parenchyma; also can get infection due to
stagnation and urine a good nutrient broth, repeated infections lead to scarring, autosomal
dominant*
Clinically: hematuria due to infections (red blood cells and red blood cells casts),
hypertension (due to scarring of BVs), liver cysts*, 20 % have berry aneurysm* of
cerebral vessels (may not know they have disease until suddenly collapse due to leakage
of aneurysm or hemorrhage), flank pain, renal stones due to repeated infections
A 45 year old male executive died suddenly after collapsing in his office. He had
complained of a severe headache and nausea earlier. Major autopsy findings include:
massive subarachnoid hemorrhage, enlarged cystic kidneys.
What is the underlying cause of his intracranial hemorrhage? Berry aneurysm
What is the nature of his renal disease? Potter Type III (Adult Polycystic Disease)
What is the mode of inheritance of this disease? Autosomal dominant
What are other types of cystic renal disease? Infantile polycystic, dysplastic kidney,
medullary cysts
Adult Onset Medullary Cystic Diseaseautosomal dominant*; corticomedullary cysts*,
shrunken kidneys*, scarred, salt-losing polyuria*, chronic renal failure beginning in
adulthood
Horseshoe kidneyfailure of kidneys to rotate and poles fuse to form a horseshoe kidney
that remains in the pelvis, may be mistaken for a pelvic tumor, stagnation of urine and
stone formation occur in the lower part of the U shape, repeated infections lead to
scarring and hypertension and impaired renal function
Associated with Turner Syndrome (USMLE World)
Benign Recurrent Hematuriasporadic or familial, prognosis is good, on EM see thin
capillary loops* (probably leak to cause the hematuria)
Alport Syndromefemales: hematuria and mild proteinuria (autosomal recessive; can get
X-linked but only manifest with mild hematuria since X-linked needs both X’s knocked
out to manifest as poorly as males; females do not go into renal failure); males:
autosomal recessive or more commonly X-linked, progress to renal failure; clinical
manifestations: ocular problems such as cataracts and dislocated lenses and hearing
problems (neurosensory loss)*Autosomal recessive defect: α3 and α4 chains of
Collagen Type IV; *X-linked defect: α5 chain of type IV collagen
Morphology: EM—lamellation of lamina densa (splitting of lamina densa) also called
“basket woven appearance”, “moth-eaten appearance”
Side note: remember α3 chain of Collagen Type IV is the antigen in Good Pasture’s
Syndrome
Renal Tumors (reviewing notes)
Hamartomasbenign angiomyolipomas (angio=blood, myo= Sm. Muscle cells, lipoma=
fat tissue)part of systemic disease called *Tubular sclerosisrhabdomyomas (benign
tumor of striated muscle (skeletal muscle)) in the heart tissue, also associated with
neoplasms of skin, heart, and brain
Renal Adenocarcinomain proximal convoluted tubules*
Predisposing factor to remember: Tobacco* (this puts people at increased risk for GI,
lungs, kidney, bladder, and pancreas cancer)
Most are sporadic
Gene implicated is Von Hippel-Lindau (tumor suppressor gene)* in both sporadic and
familial cases of clear cell carcinoma, familial type is without symptoms; the gene is
lost, inactivated, or hypermethylated
Hereditary papillary carcinoma: autosomal dominant*, mutation in MET protooncogene*, Trisomy 7*, usually bilateral; CP: painless hematuria*; Lab findings:
polycythemia* (tumors secrete erythropoietin), hypercalcemia* (causes constipation,
people act funny as causes mental issues), feel itchy all over, feel flushed all the time,
very high Hbg and Hct
How to differentiate Hereditary papillary carcinoma from Polycythemia rubra vera? In
the latter, EPO is very low
Clear cell carcinomas are the most common renal adenocarcinomas
Sporadic papillary carcinoma: papillary growth pattern, *trisomy 7, 16, 17*, Loss of
Y* (in male patients), mutated, inactivated MET*; chromosome 7 encompasses MET*, a
protooncogene that serves as a tyrosine-kinase receptor for hepatocyte growth factor,
scatter factor, which mediates growth, cell motility, and invasion (targets epithelial and
endothelial cells)(on Boards), *multifocal and bilateral, spread through renal vein*
Wilms Tumor
- peak age 2-5 years old, the younger the child at diagnosis, the better prognosis;
can be completely cured by surgery, radiation, and chemo
- Associated with 3 syndromes
o WAGR Syndrome: Wilms Tumor, Aniridia (no iris in eyes), Genital
Anomalies, Mental Retardation; deletion of 11p13 tumor associated gene
WT1
o Denys-Drash Syndrome: gonadal dysgenesis, diffuse mesangial sclerosis
(mesangial cells are specialized smooth muscle cells around blood vessels
in the kidney that help to modulate blood flow)renal failure,
gonadoblastoma (tumors of gonads), Wilms Tumor
o Beckwith-Wiedeman Syndrome: organomegaly, macroglossia (unusual
enlargement of the tongue), hemihypertrophy (enlargement of one side of
the body)
- Sporadic cases associated with mutation of *β catenin gene* (in adherin junctions
and connects to actin skeleton)
- Cells of embryonic origin are displaced in kidney and grow and differentiate into
various types of tissue
- Lab findings: erythropoietin levels are elevated (used to monitor therapy,
recurrence, metastasis)
- Micro: epithelial abortive glomeruli* (non-functional), stromal rhabdosarcoma*
(stromal malignant skeletal muscle cells), embryonal*
Assessment of Renal Function (reviewing notes)
Urinanalysis (know these):
- colorless: dilute urine (if not bc well-hydrated, think tubular disease* as cause of not
reabsorbing a lot of water), low specific gravity
- red: hemoglobin, myoglobin (blood)
- black: melaninmetastatic melanoma
Specific gravity:
Low specific gravity diabetes insipidus and tubular diseases
High specific gravity diabetes mellitus and dehydration
*pH variable with diet: pH of 7 or less, uric acid crystals will be present*
Nitritesbacteruria (infection)* partner
Proteinuria (per 24 hours): MUST KNOW THESE
1+: 250-500 mg
2+: 500-1000 mg
3+: 1000-2000mg
4+: >2000mg –nephrotic syndrome
Microscopic Examination:
Casts:
-RBCs Acute Nephritic Syndrome
-WBCsAcute Pyelonephritis
-Granular (broken RBCs)Acute Nephritic Syndrome
-HyalineChronic Renal Disease
-TubularAcute Tubular Necrosis
-Oval Fat Bodies (tubular cells filled with lipid)nephrotic syndrome
Obstructive Pulmonary Diseases
Dyspneacommon feature of obstructive pulmonary diseases
Cigarette smokingbronchitis and emphysema
Paroxysmal reversible obstructionasthma
Mucous gland hyperplasia, hypersecretion, tobacco smoke, productive coughchronic
bronchitis
Alveolar dilation, scarring bc of severe or chronic infections, cough, purulent sputum,
feverbronchiectasis
Smooth muscle hyperplasia, excess mucous, inflammation, episodic wheezing, cough,
dyspneaasthma
Air space enlargement and alveolar wall destruction, acinus involvement,
tobacco smoke, dyspneaemphysema
inflammatory scarring/obliteration of bronchioles, tobacco smoke, air pollutants, cough,
dyspnea Small-airway disease bronchiolitis (beginnings of emphysema)
persistent cough with sputum production present for at least 3 months per year and for at
least 2 consecutive yearsclinical diagnosis of chronic bronchitis
increased Reid Index (thickness of mucous gland layer/thickness of wall between
epithelium and cartilage)Chronic Bronchitis
Cor Pulmonale with heart failureChronic bronchitis
In class review:
Cyanosischronic bronchitis
Smokingemphysema and chronic bronchitis
Pizzalpha 1 antitrypsin deficiency
Liver cirrhosisalpha 1 antitrypsin
Wheezingobstructionasthma (a lot +++++) and chronic bronchitis (++)
Barrel chestemphysema
Pneomonectomycompensatory hyperinflation
Viral infectionintrinsic asthma
Eosinophils spiutmasthma
Increased reid indixchronic bronchitis
Hyperplasia of the submucous glandschronic broncthitis and asthma
Curshmann spiralsasthma
Charcot leyden crystals-->asthma
Hypertrophy of sm masthma
Emphysema <40yoalpha 1 antitrypsin deficiency
ADAM33 polyasthma
YKL40chitinaseasthma
InfertilityCF
Steatorhhea and increased NaCl in sweat and repeated respiratory infectionsCF
Fouls smelling sputumbronchiectasis
Metalloproteinase familyADAM33
Increase IgEatopic asthma
Cor pulmonale-->chronic bronchitis (+++++) emphysema (++)
Diffuse infiltrative lung diseases:
Dyspnea, crackles (rales), no wheezing, reduced total lung capacity, x ray: honey comb
lung (end stage), fibrosis of lung: pulmonary hypertension and cor pulmonale (end stage)
Alveolitisearliest manifestation of diffuse infiltrative lung disease (restrictive lung
disease)
Egg shell calcifications of lymph nodesSilicosis
Increased risk for tuberculosissilicosis
Amphibole asbestosmesothelioma
Amiodorone (an antiarrhythmic drug)Pulmonary fibrosis, microvesicular steattosis of
the liver, and hypothyroidism
Radiationalveolitisrestrictive lung diseases
Diffuse interstitial lung disease partnership review in class
Alveolitisrestrictive lung diseases
Caplan syndromeRA and pneomoconiosis
Amiodarone (an antiarrhythmic)lung fibrosis, hypothyroidism, microvesicular steatosis
(small tiny fat droplets) of the liver *Know all of them—check TSH before putting pt on
this drug
Macrovesicular steatosisalcohol associated (big fat globs)
Reticular nodule lesions consistent with Honeycomb lungend stage of restrictive lung
disease
Amphibole fibersbrittle, straight, short asbestos fibers (break and scatter and cause
damage)pathogenic for mesothelioma
TBsilicosis (silica suppressed cell mediated immunity and inhibits ability of
macrophages to kill ingested microbacteria)
Hypercalcemiasarcoidosis (that we’ve talked about so far—will have another
tomorrow)
Anti GM-CSFalvelor proteinosis
Genetic is a mutation in the same factor (GM-CSF)
Quartzsilicosis
Impaired surfactant clearancealveolar proteinosis
Egg shell calcifications in lymph nodes on x-raysilicosis (online also said CWP)
Chitinasesasthma (YKL40 tells about prognosis)
Metalloproteinases in asthma ADAM 33 polymorphism
Mucous plugs asthma (curschmann)
Pleural plugsasbestos
Raynaud’s phenomenen and shortness of breathscleroderma, fibrosis of lungs
A shipyard worker 65 yo comes in with dyspnea and fatigue for 6 monthsasbestosis
(do chest x rays and find asbestos fibers)
A 35 yo lady comes in with painful nodules on her legs for 3 months. Also her eyes have
been itchy and watery. She also has recurrent viral infectionssarcoidosis, recurrent
viral infections bc no CD4 bc consumed in the granulomas, check ACE and do a chest x
ray.
Atelectasis of the lung, acute lung injury, and diseases of vascular origin lecture review in
class:
Hyaline membrane (fibrin) in alveoliARDS
UremiaARDS
Hypoxia refractory to oxygen*ARDS
Sepsis a cause ofARDS
Fracture femurfat embolism
Criminal abortionair embolus
Lines of Zahn*premortem clot (2 lines: 1 line of fibrin (light pink) and 1 line of RBCs
(dark red)
Increased LD3pulmonary infarct
wedge shapepulmonary infarct
Brown induration (severe congestion)mitral stenosis
BMPR2 mutationprolif of sm m in pulmonary vasculatureprimary pulmonary
hypertension*
Normal BMR2 inhibits prolif of sm. Mm.
Necrotizing granulomaswegeners
NSAIDsasthma
Pizzalpha antirrypsin
Blue bloaterschronic bronchitis
Pink puffersemphysema
Vignettes:
65 yo lady with a hx of RA develops silicosis after retiring from a glass factory
Dx: Caplan Syndrome *
70 yo male presents with dyspnea for 6 months, chest x-ray reveals honeycomb lung*
Dx: end-stage restrictive lung disease*
Pathogenesis: alveolitis*
8 yo boy playing with marbles with his cousin. His cousin pushes him. 2 days later
develops he develops dyspnea auscultation reveals markedly diminished breath sounds
Dx: obstructive atelectasis
X ray: mediastinum shifted toward affected lung
35 yo F with progressive dyspnea, leg edema, hemoptysis and discomfort in rt upper
quadrant
Dx:primary pulmonary htn, cor pulmonale as a result
Pathogenesis: mutation of BMPR2*
65 yo construction worker with chest pain, recurrent pleural effusion* and dyspnea* for 3
months chest x ray reveals pleural opacities
Dx: mesothelioma
*pleural plugs alone do not cause these
Bx of pleura reveals malignant cells
Partnership Reviews in Class:
A young African American woman comes in because she has had recurrent renal colic
(sharp pain in the lower back that radiates to the groin) and hematuria. Now she also
reports shortness of breath.
No rash
No hemoptysis
No scleroderma
DDx: Sarcoidosis, bc lung and kidney involvement but no hemoptysis
The reason she has colic is because she has high calcium and thus calcium calculi in the
kidney. Pts don’t always have to have constipation.
X ray: in the lungs, nodular lesions
In mediastinum, see hilar lymph nodes
If biopsy, will see non-caseating granulomas
A 60 yo male heavy smoker presents with left eye ptosis and dry skin on the left side of
his face
Dx: Horner’s Syndrome
Pathogenesis: Lung cancer invading sympathetic ganglia
Check: Do chest x ray to find a mass
A 55 yo male presents with htn, recent onset diabetes, and a round swollen face. He has
been smoking for 30 years.
Dx: Cushing’s Syndrome
Underlying problem: elevated ACTH coming from small cell carcinoma
A 26 yo man presents with productive cough for 4 months. The sputum is mucinous.
Dx: Bronchioalveolar carcinoma
Bx: a papillary tumor lined up by tall columnar cells
A 55yo man presents with flushing, diarrhea, and a new murmur consistent with tricuspid
valve damage.
Dx? Carcinoid Syndrome
EM? Bx of tumor will show neurosecretory granules
A 75 yo male dies suddenly after a surgery for a broken femur.
Dx: Fat embolism
A 22 yo tall slender man presents with sudden onset of dyspnea and chest pain. Chest
exam reveals decreased breath sounds. X ray reveals a collapsed left lower lobe. The
trachea is pushed away from the collapsed lung.
Dx: Spontaneous pneumothorax, secondary to peripheral emphysema that occurs in
young people called Paraseptal Emphysema
Some new and old partnerships…
Endothelial injury ARDS
SIADH paraneoplastic syndrome of small cell carcinoma
Gelatinous sputumalveolar proteinosis*GMCSF mutation or loss caused by
antibodies*
Deep leg veinsthromboembolismcan cause a PE
Air fluid levelabscess
Lambert EatonautoAbs against neuronal Ca2+ channels and they have muscle
weakness that improves when use the muscles (in contrast with Myasthenia Gravis where
the muscle weakness gets worse when you use the muscle)
Virchow nodesupraclavicular node invaded by gastric or lung cancer
cannot be resectedsmall cell carcinoma
Dexamethasone suppression testdifferentiates between ectopic cancer producing
ACTH (doesn’t suppress) and pituitary cancer causing Cushing Syndrome where it does
suppress the ACTH
Elevated Reid IndexChronic Bronchitis
Peripheral tumor of the lungadenocarcinoma
Sharp chest painpleuritis
Shortness of breathpleural effusion
Lines of Zahnpremortem clot
Erythema nodosumsarcoidosis
Lamellar bodies in the sputumalveolar proteinosis
Head and Neck Pathology
Make enamel resistant to degradationfluoroapatite (from fluoride)
Chronic alcoholics, homeless, bacillus fusiformis, poor dental hygienerisk factors for
gingivitis
Hyperplastic gums (swollen gums)phenytoin and AML5 (monoblastic leukemia)
Periodontitis (inflammation of periodontal ligament, cementum, and
bone)actinobacillus and actinomycetes
Periodontitisimmune system impairment: e.g AIDS, Leukemia, Diabetes, Neutropenia
Periodontitis can cause infective endocarditis, pulmonary abscess, and brain abscess
An erythematous, hemorrhagic, exophytic mass on the gingival mucosa of a pregnant
womanpyogenic granuloma
(pygogenic granuloma looks like granulation tissue (not granuloma—no giant cells)
under the microscope. Reminder that granulation tissue consists of neovascularization,
fibrosis, and lymphocytic infiltrates)
A single painful ulceration of the mouth mucosa with an erythematous halo surrounding a
yellowish fibrinopurulent membrane in a woman who is stressedapthous ulcer (canker
sore)
Beefy red tongueglossitis
B12 deficiency (e.g. Pernicious Anemia), Celiac Sprue, Kawasaki Disease, PlummerVinson SyndromeGlossitis
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001984/ (reminder of Kawasaki)
Macroglossia (large tongue)children (Cretinism—congenital hypothyroidism; and
Pompe Disease—Acid Maltase deficiency, a lysosomal storage disease) and Adults:
Cmyloid (Amyloidosis—kidney problems: nephrotic syndrome manifesting as edema of
legs and foamy urine; heart failure: dyspnea and leg edema)
Herpes Simplex virus, recurrent vesicular lesionscold sores
White lesion that can be scraped and goes away with tx; associated with
immunosuppression, diabetes, and AIDScandida albicans (Thrush)
White thickening of the epithelium that cannot be scraped, precancerousleukoplakia
Raspberry tongueScarlet fever
Strawberry tongueScarlet fever
Koplik spotsMeasles
Dirty white suppurative membrane over tonsilsDiptheria
Red vesicular lesions in mouth after antibioticerythema multiforme (Stevens-Johnson
Syndrome)
Ludwig angina (cellulitis of the neck)pancytopenia that leads to gingivitis, pharyngitis,
and tonsillitis
Enlargement of the gingivamonocytic leukemia (AML5)
Striking fibrous enlargement of the gingivaephenytoin (Dilantin) ingestion
Multiple congenital aneurysmal telangiectasis beneath mucosal surfaces of the oral cavity
and lipsRendu-Osler-Weber Syndrome
Smoking, Alcohol, and HPVrisk factors for Squamous cell carcinoma of the mouth
Mutations that cause hyperplasia/hyperkeratosis + mutation of p53 causing
dysplasiasquamous cell carcinoma of the mouth
Necrotizing lesions of the nasal cavity and sinusitisWegener’s granulomatosis
Sinusitis in diabeticsmucormycosis
HPV 6, 11squamous papilloma of the nasopharynx
Virus found in nasopharyngeal cancerEBV
Tx for nasopharyngeal cancerradiotherapy (50-70% 3-year survival, undifferentiated,
unkeratinized the most sensitive)
H. influenzae, β-hemolytic Strep, parainfluenzalaryngoepiglottitistrouble breathing
and barking cough (croup)
Hoarseness of voice in a singersinger’s nodules
Tobacco use, persistent hoarseness, later dysphagia, pain and hemoptysissquamous cell
carcinoma of the larynx, keratinizing
Swelling of the parotid glandMumps (an RNA virus)
In children, no sequelae from Mumps
Pancreatitis and Orchitissequelae from Mumps in adults
Sialolithiasisbacterial sialadenitis
Anti-SSA (anti-RO) and Anti-SSB (anti-La), dry eyes and mouth, risk for
lymphomaautoimmune Sjogren Syndrome
Anti-RO (anti-SSA)intrauterine heart block of fetus
Mixture or epithelial cells and myxoid connective tissue that forms a benign tumor of the
parotid glandPleomorphic adenoma
Most common benign tumor of the parotid glandpleomorphic adenoma
Tumor comprising of glands and lymphocytesWarthin tumor (papillary cystadenoma
lymphomatosum)
Second most common benign salivary gland tumorWarthin tumor (papillary
cystadenoma lymphomatosum)
Most common malignant salivary gland tumor with squamous cells, mucus-secreting
cells, and intermediate cells of varying differentiation (majority in
parotid)Mucoepidermoid carcinoma
parainfluenza virus croup [epiglottitis]
EBV nasopharyngeal carcinoma
HPV oral cancer, laryngeal papillomas
GlossitisB12 deficiency, Kawasaki, Plummer-Vinson, celiac sprue
Mumpsorchitis
P53 mutationoral cancer
Mucormycosisdiabetes
Facial palsymalignant tumor, parotid gland, resection of benign parotid tumor
Macroglossiachildren (cretinism/Pompe), adult (amyloid)
Vignette: A young vagrant with foul gums: a 19 year old male, a homeless vagrant, is seen in the
ED in a drunken state. He is bleeding from the mouth but has no history of trauma. On
examination there is acute sloughing and ulceration of the gums surrounded by an inflamed red
mucosa w/ many areas of bleeding. The breath is foul & the teeth are dirty, with a large build
up of plaque & calculus. A smear from the ulcerated areas shows numerous fusiform &
spirochaetal organisms
Diagnosis: gingivitis
Predisposing factor: poor oral hygiene
Organisms: Bacillus fusiformis
Long-term complications: ulceration of mouth,
necrosis
Vignette: A 72 y/o retired bookbinder is referred by his dentist because of an area of white
thickening of the buccal mucosa. On examination, there is an ill-defined thick white patch on
the buccal mucosa on the left (cannot be scraped off)
Diagnosis: leukoplakia
Why biopsy: to rule out cancer (this is a precancerous
lesion)
Vignette: A retired doctor aged 74 - area of white thickening on lateral border of anterior third
of tongue; smoked many years, alcohol. Describes lesion as slowly enlarging thick white patch
present for many months
Diagnosis: carcinoma
Biopsy: squamous cell carcinoma
Spread: will go to cervical lymph nodes
Vignette: 57 y/o woman w/ smooth enlarging mass at angle of jaw on left side. Has been
present for some years, no trouble but slowly enlarged & now disfiguring. Her daughter fears
cancer & lump can no longer be disguised; appears to be in parotid gland
Diagnosis: pleomorphic adenoma
Precautions during surgery: facial nerve
Vignette: "Singer w/ hoarse voice"
Diagnosis: singer's nodule
Vignette: An old man w/ loss of voice: 68 M, pig farmer, heavy smoker, has had hoarse voice for
as long as can remember; complete loss of voice 1 month; left vocal cord replaced by large
white friable mass
Diagnosis: squamous cell carcinoma of larynx
Pathology of the Esophagus
Upper esophageal webs, iron deficiency anemia, glossitis, and cheilosisPlummer-Vinson
Syndrome
Risk of post-cricoid carcinomaPlummer-Vinson Syndrome
Vignette: a 30 yo man comes in tired, pale, bothered by dry, cracked lips. CBC shows iron
deficiency anemia (microcytic anemia), red beefy tongue (glossitis), upper endoscopy shows
esophageal webs
Dx: Plummer-Vinson Syndrome
Zenker (Pharyngeoesophageal) Diverticulumdiverticula immediately above the UES;
associated with accumulation of food in diverticula and regurgitation, dysphagia, a neck mass,
and aspiration pneumonia
Diverticulum located above LES, nocturnal regurgitation of massive amounts of food when lie
downEpiphrenic Diverticulum
Longitudinal treats at the esophagogastric junction or gastric cardia, commonly seen in
alcoholics in binge drinking with severe retching or vomiting, severe pain and vomiting blood bc
tore mucosaMallory-Weiss Syndrome
Pain to back and vomit bloodBoerrhaave syndrome (perforated GI tract, esophagus)
Prolonged or severe portal hypertensionblood diverted through coronary veins of stomach
and submucosal venous plexusincreased pressure in plexusvarices
Alcoholic cirrhosisesophageal varices (if rupture, massive hematemesis and up to 50% die in
first bleeding episode)
Heartburn, dysphagia, in severe cases: hematemesis and melenareflux esophagitis
Ulceration, stricture, Barrett espophagus, bleedingbad clinical outcomes of reflux esophagitis
Metaplastic change in which squamous epithelium of esophagus is replaced by columnar
epithelium with goblet cells (intestinal metaplasia)Barrett Esophagus
Long-standing GERDBarrett Esophagus
Barrett Esophagus is single most important risk factor for? esophageal carcinoma
Squamous cell carcinoma of esophagus risk factorsin US, alcohol and tobacco; in other
countries, fungi and nitrosamines
Dysphagia predominant sign with weight lossadenocarcinoma
Insidious onset with late development of dysphagia, obstruction, cachexia,
debilitationsquamous cell carcinoma of esophagus
Review:
EBVnasopharyngeal carcinoma
Koplik spotsMeasles
Ludwig angina (severe inflammation of buccal mucosa with cellulitis (severe swelling) of the
neckpancytopenia (see in patients on chemo)
Bacillus fusiformis (poor hygiene, alcoholics)gingivitis
Pregnancypyogenic granuloma
Dirty membrane on tonsils, fever, difficulty breathingdyptheria
Plummer-Vinson Syndromecheilosis, upper esophageal webs, iron deficiency anemia
Nocturnal regurgitation of large amt of fluidepiphrenic diverticulum
Barrret esophagusintestinal metaplasia of the lower esophagus; associated with
adenocarcinoma of the esophagus
HPVnasopharyngeal papilloma (benign lesions)
Stressaphthous ulvers
Diabetesmucormycosis especially of sinuses
Chaga’s diseaseachalasia
Singer’s nodulereactive nodule (another name)
Esophageal varices portal hypertension
Coronary veinsesophageal submucosal venous plexusvarices (pathway of blood from liver
to esophagus)
Longitudinal mucosal tear of the esophagusMallory-Weiss Syndrome
Vignette: binge drinking and then vomit forcibly and mucosa tears up; if also pain in back, they
ruptured their esophagus Boerrhaave
Boerrhaaverupture esophagus
Parainfluenza viruscroup (epiglottitis)—cannot breathe and seems to be choking (Haemophilis
inf also, but not as common)
Kawasakiglossitis
Orchitismumps in adults
Most common tumor in salivary glandspleomorphic adenoma (myxoid stroma)
Intrauterine fetal heart blockanti-Ro with Sjogren syndrome in mother
Pathology of the stomach
Antiparietal cell antibodiesautoimmune gastritis
Congenital hypertrophic pyloric stenosisOlive like mass, projectile vomiting, 2-3 wks old,
Turner Syndrome, visible peristalsis
Pernicious anemiaautoimmune gastritis
NSAIDSdecreased prostaglandinsacute gastritis and peptic ulcers and chronic interstitial
nephritis
NSAIDS, excessive alcohol consumption, heavy smokingacute gastritis
Pathogenesis of acute gastritis:
Increased acid secretiondecreased HCO3-decreased blood flowdisruption of mucous
layer + direct mucosal injuryacute gastritis
Massive hematemesis in alcoholicsesophageal varices, acute gastritis, Mallory-Weiss
Syndrome
Antral chronic gastritisHelicobacter pylori (90%)
Autoimmune gastritisantibodies to parietal cells, gastrin receptor, intrinsic factor, and H+K+
ATPaseachlorhydria, pernicious anemia, atrophy of the mucosaHIGHER risk for gastric
carcinoma if pernicious anemia present
Chronic gastritislymphocytes and plasma cell infiltrates; if neutrophils present, there is active
inflammation
Chronic gastritis due to H. pylorihypochlorhydria, not achlorhydria bc not all parietal cells are
destroyed
Autoimmune gastritishypergastrinemia
H. pyloririsk of chronic gastritis, peptic ulcer, gastric carcinoma, MALT lymphoma
Prostaglandin synthesis by mucosal cells (COX inhibitors remove these protective
effects)increased mucus and bicarbonate production, vasodilation and improved mucosal
blood flow, inhibits acid secretion by parietal cells
Antral type gastritis caused by H. pyloriincreased acid production and increased risk of
duodenal ulcer
Pangastritis caused by H. pyloriatrophy
Zollinger-Ellison Syndromemultiple peptic ulcers in the stomach, duodenum, and jejunum due
to excess gastrin secretion by a tumor (gastrinoma)
Curling ulcersassociated with severe burns or trauma
Cushing ulcersassociated with intracranial injury, operations or tumors
Intracranial injurydirectly stimulate vagal nuclei, leading to increased acid production
Phytobezoarsconcretions of plant matter in the stomach
Trichobezoars “hairballs” in the stomach
Menetrier’s disease (a type of Hypertrophic Gastropathy)males in the 4th-6th decades,
hyperplasia of mucous cells, with atrophy of glandsexcessive mucous causes loss of protein in
feces and thus hypoproteinemia
Hyperplastic polypsno malignant potential
Adenomasmalignant potential
Nitrites, smoked and salted foods, pickled vegetables, deficiency of fresh fruits and vegetables,
cigarette smokinggastric carcinoma
Mutations in CDH1E-cadherinrisk for gastric cancer
Loss of E-cadherindiffuse gastric carcinoma
BRCA2 mutationsdiffuse gastric carcinoma
Large portion of gastric wall or entire stomach infiltrated with malignancy, “leather bottle”
appearanceLinitis Plastica
Intestinal type histologymutations in β cadherin and APC
Gastric type histologyinfiltrating pattern of poorly differentiated cells with “signet ring”
conformation (cells full of mucus with nucleus pushed to the side)
Virchow’s node (supraclavicular node)lump in neck due to mets from gastric or lung
carcinoma
Krunkenberg Tumorsmets to ovaries from gastric cancer
Sister Mary Joseph nodulemetastatic nodule that appears in paraumbilical region
MALT Lymphoma (lymphoma of mucosa-associated lymphoid tissue)11;18 translocation
Gastrointestinal stromal tumormutation of the gene encoding tyrosine kinase (cKIT)
Gastrointestinal Carcinoid Tumors
-most common in the jejunum/ileum
-patients typically in 50s-60s
-all secrete serotonin
-in stomach, MEN-1 mutation
-in proximal duodenumCCK (cholecystokinin) causes biliary obstruction and abdominal pain;
also associated with Zollinger-Ellision Syndrome and NF-1 (neurofibromatosis-1)
-in jejunum/ileumpolypeptide YY also secreted which causes constipation; aggressive
behavior
-in appendixmostly an incidental finding bc asymptomatic, benign behavior
Crohn’s
Skip lesions
Transmural
granulomas
fistulas and strictures
cancer+
Ulcerative colitis
Continuous –rectum then up
mucosal
crypt abscess
cancer+++
superficial
Review in class:
Krunkenberg tumormetastatic signet ring gastric tumor to ovary
AdhesinsH.pylori
Multiple gastric ulcersZollinger-Ellison Syndromevery increased gastrin
Protein-losing gastropathy, diarrheaMenetrier’s Disease
Linitis plasticainfiltration of all layers by gastric carcinoma
Head injuryCushing ulcer
Burnscurling ulcer
Pain boring to backperforated peptic ulcer
Blood group Acarcinoma of stomach
Urea breath testH. pylori
Zenker Diverticulumupper esophagus
NSAIDSpeptic ulcers
Pathology of small intestine
Contains all 3 layers of normal bowel wall (true diverticulum)Meckel Diverticulum
Osmotic diarrhea (osmolality exceeds that of the plasma)lactasae deficiency (lactose
intolerance)
Several bowel movements, bulky, fat, foul-smelling, floats, weight loss,
anorexiaMalabsorption
Celiac Sprue, Crohn’s Disease, pancreatic insufficiencyMalabsorption syndrome
Rotavirusoutbreaks of infectious enterocolotis in infants
Norwalk virusesoutbreaks in school children and adults
Adenovirusesoutbreaks in infants
Astrovirusesoutbreaks in children
Vibrio choleraewater borne enterotoxinsecretory diarrhea
S. aureusquick onset, food-poisoning (pre-formed toxin), e.g. egg salad at party and
everyone who ate it became sick
Salmonella and shigellainvasive bloody diarrhea
Typhoid feverdiarrhea or constipation
Giardia lambliamalabsorptionsteattorhea
Entamoeba histolyticadysentery (pain, blood, low volume)
Radiationendothelial cell injuryischemic fibrosis and stricture
Clinical Vignette: 31 yo male with an itchy vesicular rash on extensor surfaces, such as
the elbow. The rash has been there for 2 weeks. On further questioning, he reports
diarrhea for 6 months (steatorrhea) and 15 lb weight loss.
Dx: Celiac Sprue
Tests: Anti-gliaden and anti-endomysial antibodies (IgA immunoglobulins, some IgG;
have to look for IgG immunoglobulins if also have IgA deficiency); Bx
Tx: improves on withdrawal of wheat gliadens and related grain proteins from diet
Pathology: Cytotoxic T-cell mediated hypersensitivity, release cytokines which damage
intestinal wall
Morphology: grossly, mucosa appears flat or scalloped, or even normal
Microscopically, diffuse enteritis with marked atrophy or total loss of villi and increased
intraepithelial lymphocytes
Hypersensitivity to wheat gluten and gliadenHLA-DQ2 and DQ8
HLA-DQ8Hashimoto’s Thyroiditis, Grave Disease, IgA Nephropathy
Clinical features: diarrhea and failure to thrive in infants but may not present with
malabsorption until adults
Dermatitis herpetiformisgranular IgA deposit in dermal papillae in response to gluten
ingestion; is characterized by intensely itchy, chronic papulovesicular eruptions, usually
distributed symmetrically on extensor surfaces (buttocks, back of neck, scalp, elbows,
knees, back).
(Dermatitis
herpetiformis from Wikipedia)
Clinical Complications: risk of *non-Hodgkin’s lymphoma, small intestinal
adenocarcinoma, and esophageal SCC
Tropical Sprue= celiac-like malabsorption syndrome in people visiting the tropics or
people of the tropics, no specific causal agent found, but enterotoxigenic organisms
implicated, responds to antibios, changes similar to Celiac, not associated with lymphoma
Whipple Disease= a rare systemic disease primarily of the intestines, joints, and CNS,
caused by gram-positive actinomycete Tropheryma whippelii; usually affects white males
(suspect associated with occupations, such as farming), lamina propria is laden with
distended macrophages, containing tiny rod-shaped bacilli that are PAS positive*;
presents with malabsorption syndrome, polyarthropathy/polyarthritis, lymphadenopathy
and hyperpigmentation of skin in >50%; cardiac and neurologica signs can also be
present, responds to broad spectrum antibiotics
Disaccharidase cleaves lactose: Disaccharide deficiencyincreased lactose in gut
lumen,osmotic diarrhea and malabsorptionbacterial fermentation of unabsorbed
lactoseincreased hydrogen production and gaseous symptoms
Abetalipoproteinemia: autosomal recessive disorder in which there is mutated MTTP
gene; “The MTTP gene provides instructions for making a protein called microsomal
triglyceride transfer protein, which is essential for creating beta-lipoproteins. These
lipoproteins are both necessary for the absorption of fats, cholesterol, and fat-soluble
vitamins from the diet and necessary for the efficient transport of these substances in the
bloodstream” (Wikipedia) ; deficiency is betalipoproteinsdecreased LDL and VLDL
and chylomicrons (betalipoproteins needed to transport VLDL and
chylomicrons)defective cell lipid membranesacanthocytes (Burr cells)
Decreased synthesis of apoproteins leads to increased TGscell vacuolization of
enterocytes seen on biopsy/microscopy
-deficiency of fat soluble vitamins (ADEK) and decreased ability to absorb fat
-infancyfailure to thrive, diarrhea, and steatorrhea
http://en.wikipedia.org/wiki/Abetalipoproteinemia
Ischemic Bowel Disease
-usually old people with atherosclerosis or young people with hypercoagulability
-can be restricted to either the small or large intestine or both
-infarctions seen with acute occlusion of celiac, superior, and inferior mesenteric arteries
-etiologies: thrombosis, embolism, non-occlusive (cardiac failure, shock, etc.), radiation
therapy, volvulus, stricture
-symptoms: severe, intolerable pain and bleeding in stoolbright red blood in stool
-50-75% death rateshort time between symptoms and perforation
-Transmural infarcts: sudden, severe abdominal pain and tenderness, can have nausea and
comiting and bloody diarrhea, shock and vascular collapse within hours, diminished
peristalsis; due to sudden occlusion of major vessels; bowel becomes swollen and
gangrenous and perforates in few days
-Mucosal and mural infarcts: may not be fatal if cause corrected, mostly due to
hypoperfusion, non-specific abdominal complaints and intermittent bloody diarrhea that
may progress to infarction and sepsis
-Chronic ischemia infarcts: mucosal atrophy, ulcerations, mural fibrosis, but not a
medical emergency; insidious with intermittent bloody diarrhea, resembling
inflammatory bowel disease
Hernias= weakness in peritoneal cavity wall results in protrusion of a pouch-like, serosalined sac of peritoneum, commonly in inguinal and femoral canals, umbilicus, and areas
of surgical scars
-segments of viscera may protrude and become trapped, resulting in ischemia
-incarceration: permanent trapping of bowel loop due to edema from impaired venous
drainage
-strangulation: compromised arterial supply and venous drainageinfarction
-incarceration and strangulation need immediate surgery
Adhesions
-due to inflammation (peritonitis) from surgery, infection, radiation, and
endometriosisas healing occurs, get adhesions between bowel loops, bowel wall, and
surgical site
-twisting around adhesions can cause strangulation and obstruction
Intussusception
-one segment of bowel telescopes into another, and peristalsis further wedges this
segment further, resulting ins ischemia
-infants—no underlying cause or can be associated with rotavirus*, usually in children
-Adults—usually an intralumenal mass or neoplasm is also present
Symptoms: pain, currant jelly stool, bleed
Tx: barium enema to push one segment out of the other or can go away on its own
Volvulus
-complete twisting of a bowel loop about its mesenteric baseobstruction and infarction
-most commonly in large redundant loops of sigmoid colon and small intestine
Pathology of Large Intestine
Blood supply (on Boards):
Superior mesenteric arteryascending and proximal transverse colon
Inferior mesenteric arteryremainder of colon to rectum
Superior hemorrhoidal branch of inferior mesenteric arteryupper rectum
Hemorrhoidal branches of iliac or internal pudendal arterylower rectum
Congenital Aganglionic Megacolon: Hirschsprung Disease
-absence of ganglion cells (in Auerbach’s (myenteric) and Meissner’s (submucosal)
plexi)) in a portion of the intestinal tract
-due to problems with neural crest cell migration or early death of ganglion cells
-leads to functional obstruction (constipation) and massive intestinal dilatation proximal
to the aganglionic segment
-complications include enterocolitis and perforation of the colon or appendix with
peritonitis
-manifests in newborns as failure to pass meconium and constipation
Acquired Megacolon
-results from Chagas disease, obstruction by neoplasm or inflammation, and as
complications of inflammatory bowel disease
-Chagas disease
-Pseudomembranous colitis
-Inflammatory Bowel Disease (broad term for Ulcerative Colitis and Crohn Disease)
Pseudomembranous colitis
-Clostridium difficile
-Toxins A and B cause host cell apoptosis (look for toxins/spores in stool)
-usually occurs secondary to broad spectrum antibiotic use for a couple of
weeksdiarrhea and dilation of colon
-may occur without antibiotic therapy: after surgery or debilitating illnesses
-plaque-like adhesions of fibrinopurulent-necrotic debris and mucus
Idiopathic Inflammatory Bowel Disease—can cause toxic megacolon by destruction
of neural plexi
-collective term for Crohn Disease and Ulcerative Colitis
-results from inappropriate and persistent activation of the mucosal immune system
-Crohn disease (AKA terminal ileitis, regional enteritis, and granulomatous colitis): noncaseating, granulomatous (50%) and can be found from esophagus to anus, most often
intestine and colon; transmural; skip lesions (segmental), granular serosa with
“creeping fat” and thick wall, mesentery also thickened and edematous; “string sign”
on x ray from narrowed gut lumen; early lesions are apthous ulcers in mucosacoalesce
into linear ulcerscobblestones; complications include fistula formation between
loops of bowel, bladder and skin, strictures, and malabsorption and protein-losing
enteropathy; intermittent attacks of diarrhea, fever, and abdominal pain separated by
asymptomatic weeks to months; may be caused by periods of physical and emotional
stress; may have occult blood loss, leading to anemia, may have severe right lower
quadrant pain; extraintestinal manifestations: migratory polyarthritis, sacroilitis,
ankylosing spondylitis, erythema nodosum, primary sclerosing cholangitis, clubbing of
fingers
-Ulcerative Colitis: nongranulomatous, confined to colon and rectum, and superficial;
continuous, slightly more common, associated with nonsmoking, particularly exsmokers; crypt abscesses lead to ulcerations that are linear and broad-based, leaving a
raw, exposed muscularis propria; dysplasia noted to give rise to adenomas or invasive
carcinoma; relapsing bouts of bloody, mucoid diarrhea, persisting for days, weeks or
months, usually accompanied by lower abdominal pain and cramps, relieved by
defecation, attacks precipitated by physical or emotional stress; complications: increased
risk for carcinomas, often infiltrative w/o obvious masses, toxic megacolon and
extraintestinal lesions, extraintestinal lesions: ankylosing spondylitis, primary
sclerosing cholangitis, erythema nodosum, pyoderma gangrenosum
-both have extraintestinal inflammatory processes associated
HLA-DR2Ulcerative Colitis
HLA-B27pts with IBD and ankylosing spondylitis (is a chronic, inflammatory arthritis
and autoimmune disease.[1] It mainly affects joints in the spine and the sacroiliac joint in
the pelvis, and can cause eventual fusion of the spine.)~wikipedia
Angiodysplasia= tortuous dilations of submucosal and mucosal blood vessels in cecum
or right colon, vascular degenerative changes normal distention and contraction of wall
may occlude the submucosal veinsfocal dilatation (elderly); manifested as variable
bleeding (some massive and severe)hematochezia (bright red blood)
Chronic constipation and straining, pregnancy (venous stasis), liver cirrhosis and
htnhemorrhoids
Focal wall weakness + increased intralumenal pressureDiverticular disease
Diets low in fiber reduce stool bulk, increase peristalsisdiverticular disease
Nipple-like protrusions into lumen of colonhyperplastic polyps
Benign tumors of blood vessels and mesenchymal tissue in children less than
5yoJuvenile Polyps
Potentially malignant juvenile polypsautosomal dominant juvenile polyposis syndrome
Multiple hamartomatous polyps of mucosa, lamina propria, and muscularis mucosa
throughout GI tract + melanotic mucosal and cutaneous pigmentation around oral
mucosa, lips, face, genitalia, and palmar surface of hands + risk of
intussusceptionPeutz-Jeghers Syndromeincreased risk of carcinoma of pancreas,
breast, lung, ovary, and uterus (polyps no malignant potential)
Most common adenomas of colontubular adenomas
Villous adenomas of rectum and rectosigmoidless common but precancerous,
hypokalemia, big bulky cauliflower like structures, very tall villi
Innumerable adenomatous polyps, autosomal dominant, mutation of adenomatous
polyposis coli (APC) gene on chromosome 5, 100% progress to
adenocarcinomafamilial adenomatous polyposis (FAP)
Variation of FAP with osteomas of mandible, skull, and long bones, epidermal cysts, and
fibromatosisGardner syndrome
Turcot syndromeademonatous colonic polyposis + CNS tumors
Players in Familial adenomatous polyposis:
APC= a tumor suppressor gene that suppresses β-catenin
β-catenin= causes cell proliferation
K-RAS= proto-oncogeneif becomes oncogene, cells don’t undergo apoptosis
P53tumor suppressor gene
Telomerase (an enzyme that adds DNA sequence repeats ("TTAGGG" in all vertebrates)
to the 3' end of DNA strands in the telomere regions, which are found at the ends of
eukaryotic chromosomes. This region of repeated nucleotide called telomeres contains
non-coding DNA material and prevents constant loss of important DNA from
chromosome ends)~wikipedia
Pathological progression of FAP:
-Hit 1= mutated APC allele inherited
-Hit 2= loss of normal APC allele
-Hit 3= K-RAS mutation
-Hit 4= loss of p53
-Hit 5= Telomerase mutation
Lynch Syndrome= hereditary non-polyposis colorectal cancer due to DNA mismatch
repair
Adenocarcinoma= most common cancer of colon
Etiology:
-excess caloric intake
-low unabsorbable vegetable fiber
-large quantities of refined carbohydrates
-red meat
-decreased intake of protective micronutrients: vitamins A, C, E
If >55 yo and iron-deficiency anemiathick cecal cancerneed colonoscopy
Adenocarcinoma of the colon metastasizes to liver (#1 that goes to the liver) (regional
lymph nodesliver, lungs and bone)
Carcinoid tumor
-appendix most common side, followed by small intestine, rectum, stomach, and colon
-solid, yellow tan appearance
-many asymptomatic, may obstruct, may be functional e.g. hyperinsulinema, Cushing
Syndrome, Zollinger-Ellison Syndrome
-May have carcinoid syndrome due to elevated serotonin: flushing, diarrhea, asthma
-may metastaze to liver
-5 year survival 90% (50% if small bowel tumor and liver mets), wide spread disease
usually results in death
RLQ pain, vomiting, fever, rebound tenderness in RLQ, CBC shows leukocytosis w/ left
shiftacute appendicitis
Obstruction by fecolithgs, gallstones, tumors or parasitesacute appendicitis
Neutrophils in the muscularis of appendixacute appendicitis
Mucinous cystadenocarcinomas of appendix implant peritoneummucin=
pseudomyxoma peritoneii (seeding of peritoneum by mucus secreting cells from ruptured
intestine or ovary)
Dermatitis herpetiformisceliac sprue
Osmotic diarrhealactose intolerance
Malabsorption and skin hyperpigmentationWhipple Disease
Lynch Syndromehereditary colon cancer non-APC, DNA mismatch repair
IgA Deposits in dermal papillaedermatitis herpetiformisCeliac Disease
True DiverticulumMeckel’s Divirticulum
Anti-gliaden antibodyCeliac sprue
Clostridium difficilePseudomembranous colitis
Transmural inflammationCrohn’s Disease
Steatorrheamalabsorption
Crypt abscessesUlcerative colitis
PAS positive macrophages in lamina propriaWhipple Disease
AntibioticsC. diffpseudomembranous colitis
Juvenile colon polyps + hyperpigmentation of oral mucosaPeutz-Jeghers
Syndromehereditary pancreatic & ovarian carcinomas
Pancreatic diseases:
Epigastric pain boring to back with vomitinglook at vomitus, if has blood, think of
perforation of peptic ulcer; if vomitus is biliousacute pancreatitis
Boerrhavesubmediastinal pain that bores to back (not in epigastic area, a little higher)
SPINK1 (serine protein inhibitor kazal 1)hereditary pancreatitis syndrome
D-xylose testdistinguishes between pancreatic or intestinal causes of malabsorption: if
pancreatic disease, d-xylose test will be normal, if intestinal disease, d-xylose test is
abnormal (give pt known quantity and check for it in urine, if intestine is NOT diseased,
will show in the urine. D-xylose absorption NOT dependent on pancreatic enzymes)
Painless SEVERE obstructive jaundice (direct bilirubin >5, Alkaline phosphatase
>500)extrahepatic obstructionpancreatic carcinoma of the head of the pancreas;
could also have Trousseau’s signmigratory thrombophlebitis and hypercoagulability
Liver tests:
Transaminases (AST, ALT), when elevated mean necrosis (intracellular enzymes have
leaked out of damaged cells)
Level of elevation tells you about pathology
If severe, in the 1000s—hepatitis (severe inflammation of liver and release of large
quantities of transaminases)
If mild damage, in the 100s—congestion of liver due to congestive heart failure
In between is moderate—in cirrhosis of liver
LDH5 elevationnecrosis of liver cells
LDH1heart and red cells
LDH3pulmonary infarction
Bilirubindirectobstruction (intra or extrahepatic)
Bilirubinindirect impaired conjugation OR hemolysis
Proteins made in liver: Albumin and Coagulation factors (PT and PTT)
Increased ammonia levelscomplete liver failuremusty odor
antiLKM (liver, kidney, microsomes)autoimmune hepatitis
hepatitis C liver morphologyfatty change
fatal in pregnant womenHep E
antibodies to HBsAg w/o any other antigens or Abseffective immunization
Low hepcidinhemochromatosis
Low ceruloplasminWilson’s Disease
High alphafetoproteinHepatocellular carcinoma
Oral contraceptiveshepatic adenoma
Vinyl chlorideangiosarcoma of the liver
Target cells on peripheral smear, microcyticcirrhosis of the liver
Miscrovesicular steatosispregnancy, amiodarone, tetracycline toxicity, Reyes
Syndrome
High ammoniahepatic failure, hepatic encephalopathy
Mallory bodiesalcoholic hepatitis
DsDNA virusHepatitis B
PAS positive intra1hepatic inclusionsalpha-1 anti-trypsin deficiency
Metastatic liver tumorsprimary is colon
Crypt abscessulcerative colitis
Signet ring cellsdiffuse carcinoma of the stomach
Krukenberg tumor when above mets to ovaries
Upper esophageal webPlummer Vinson Syndrome
Anti H+K+ ATPaseautoimmune gastritis
FistulasCrohn’s
Osmotic diarrhealactose intolerance
GastrinomaZollinger-Ellison Syndrome (multiple ulcers and diarrhea)
EBVnasopharyngeal carcinoma
Budd Chiari + anemiaPNH
HHHHemochromatosis, HFE, Hepcidin
Colonic polyps + osteomasGardner Syndrome
Juvenile colon polyps, familial ovarian cancer + hyperpigmentation of oral
mucosaPeutz Jeugher
AST>ALTalcoholic liver disease
Vignette: a tattoo artist presents to her PCP with malaise and dark urine for 5 days. She
also says she felt tired for the last 4 weeks.
DD Hep B,
Tests HBsAg, HBeAg (no Abs yet bc too early)
Risk factorsneedles
ComplicationsChronic hepatitisCirrhosisHepatocellular carcinoma (3 Cs are
complications)
Vignette: 15 yo male presents with difficulty concentrating and he reports that he has
been falling down frequently when he climbs stairs. His right upper quadrant feels funny.
DD: Wilson Disease
Tests: preliminary tests: ceruloplasmin will be low, confirmatory test: copper in the liver
(how much copper per gram liver weight)
Vignette: 6 yo girl presents to ER with stupor & vomiting for 12 hours. She has a strep
throat 5 days ago with fever. Then Mom gave her aspirin to get her fever down.
Dx: Reyes Syndrome
Tests: ALT = 500, ammonia elevated, blood glucose low; liver biopsy finding=
microvesicular steatosis
Vignette: 72 yo woman presents with diarrhea and muscle weakness for 3 months. Stool
exam reveals large amounts of mucin.
DD: villous adenoma of the colon; hypokalemia is cause of muscle weakness
Colonoscopy
Vignette: 35 yo actress presents to her PCP very concerned about severe dryness around
her lips, which she cannot mask with make up. She also reports she has been very tired
lately. On PE, her tongue is unusually red
DD Plummer Vinson
Test iron deficiency (Fe+ CBC)
What to do next: endoscopy to see esophageal webs
Vignette: Grandma Smith brings in little Jack (6 months). She is worried he had six
loose stools in the last 24 hours.
What organism: Rotavirus
Vignette: 24 yo male presents with mild jaundice and a slightly enlarged liver. He
reports that his uncle died at age 35 with some kind of lung disease. The patient also
reports that he runs out of breath when he climbs stairs to his 4th floor apt. PE:
hyperresonant chest, RR 22; labs AST and ALT are both elevated (>250); bilirubin 4,
split 50/50
DD: alpha-1-antitrypsin deficiency
What would you see on chest xray: emphysema
On liver biopsy: PAS positive intrahepatic inclusions
32 yo male with a known history of ulcerative colitis presents with recurrent rt upper
quadrant and fever and what he calls a funny color to his skin.
PE: tender right upper quadrant
very slight jaundice
test very increased IgM (hypergammaglobulinemia)—starts as an acute inflammation,
which is why IgM is increased
Dx: primary sclerosing cholangitis
Inflammation and fibrosis that obliterates intrahepatic and extrahepatic bile ducts.
Segmental constriction of ducts gives beaded appearance to barium columns on x ray
Morphology: onion skin fibrosis around the ducts= primary sclerosing cholangitis
Anomalies of the biliary tree
Von Meyenberg complexes
Polycystic kidney disease
45 yo Norwegian lady with rt upper quadrant pain radiating to her scapula. She has
been hospitalized 10 times when she had her 10 babies one year apart
PE tenderness, guarding, rebound
5 Fs are risk factors: Female, fat, fertile, forty, fair
Hemolytic anemias (chronic) would be associated with gall stones
GI Summary Partnerships:
White plaques in mouth that can be scraped offthrush
White plaques in mouth that cannot be scraped offleukoplakia
EBVnasopharyngeal carcinoma
Chronic Hep B& hematemesisesophageal varices due to portal htn
Diarrhea in babiesRotavirus
Diarrhea in childrenNorwalk virus
Explosive diarrheaLactose intolerancelactase (disaccharidase)
Fatty diarrheamalabsorption
Watery diarrheaVIPoma
HypokalemiaVIPoma and Villous Adenoma
HyperkalemiaDKA
Onion skin fibrosis of bile ductsprimary sclerosing cholangitis
HemochromatosisHFE mutation and loss of proper Hepcidin expression
SPINK1 mutationsHereditary pancreatitis syndrome
Clinical Lab Medicine Partnerships:
A 44 yo lady presents with severe right upper quadrant pain for 2 hours (pain= 10/10).
She has also had a history of chronic normocytic anemia for as long as she can
remember.
Dx: PNH (chronic normocytic anemia), pain is most likely Budd-Chiari (thrombosis of
hepatic vein)
Test: Flow Cytometry for CD55 and CD59 (cells should be negative for these)
55 yo African American lady presents with malar rash and photosensitivity for 2 weeks.
She has a hx of htn for 3 years. ANA is 1:80 homogeneous pattern, low titer
Dx: Drug-induced Lupus—she has hypertension, so should ask if she has been on
hydrochlorothiazide; If she had autoimmune lupus, the ANA pattern would have been
speckled or peripheral and the titer would have been much much higher. Homogeneous
pattern is anti-histone.
Tests: dsDNA—negative; skin bx—no specific changes; UA—normal
A patient and tell them not to eat bananas bc we are running a certain test carcinoid
tumor test (bananas increase serotonin)
Abstain from onions for testthey decrease insulin response to glucose
Increased gamma GTalcohol
Increased osmotic fragilitycongenital spherocytosis
Autosplenectomysickle cell
Bite cellsG6PD deficiency
Dry tapaplastic anemia, hairy cell leukemia, megaloblastic anemia
Pure red cell aplasiathymoma
Teardrop cells on peripheral bloodmyelofibrosis
Heat stabile alkaline phosphataseliver
6 yo boy is brought to ER by grandma who was babysitting for him. He is lethargic, he is
vomiting, and Grandma said he had a fever 5 days ago, and she did not have Tylenol, so
she gave him baby Aspirin.
Dx: Reyes Syndrome
Tests: ALT (↑), Ammonia (↑), and blood glucose (hypoglycemic)
55 yo male presents with gynecomastia, slight jaundice and ascites. AST 350, ALT 150,
AP 200.
Dx: Alcoholic cirrhosis (AST more than double the ALT)
Caffeine increases catecholamines, triglycerides, and serum gastrin and decreases
cholesterol
High CEAGI cancer, smoker, chronic hepatitis, chronic pancreatitis
Thiazideshypokalemia and induction of SLE +ANA anti-histone (drug-induced lupus)
Newbornhigh Hb, lymphocytes, bilirubin, low glucose (low glycogen reserves)
CPK higher in blacks
Albumin higher in whites
Lipids lower in Asians
Conjugated hyperbilirubinemiasRotor syndrome and Dubin-Johnson Syndrome
Mutations in UGT promoter, decreased UDP glucoronyl transferase, impaired
conjugation, auto recessive, usually asymptomaticGilbert Syndrome
Absent UGTCrigler Najar Type Ikernicterus and death in infants
Decreased UGT, managed by barbituratesCrigler Najar Type II
Continue later on p.234
Dermatopathology:
WhealHive (edematous erythematous dermal swelling)type I hypersensitivity
reaction (IgE mediated mast cell degranulation)urticaria
Granular IgG and C3 at dermal epidermal junctionSLE or Discord LE
Linear IgG at the dermal epidermal junctionBullous pemphigoid
IgA at Dermal PapillaeDermatitis herpetiformis (see in Celiac Sprue)
Intercellular IgG in the basal layer of the epidermispemphigus vulgaris
Munro abscesspsoriasisIBD
Koebner phenomenonrecurrence of the lesion at the site of the original injury
Elastosissenile or actinic (UV damage)
Suprabasilar vesicles or bullaepemphigusintercellular IgG at the dermal-epidermal
junction
Subepidermal bulla at tip of dermal papillaDermatitis herpetiformisIgA at dermal
papillae
Aging changes:
Atrophy of epidermisincreased shear force injury (senile purpura)
Decreased langerhans cellsdecreased immunityincreased risk of malignancy
UV radiationpyrimadine dimers in DNA of keratinocytes, proliferation of melanocytes
for increased melanin (can lead to melanoma), decreased langerhan cell function
(decreased immunity), abnormal elastin production (solar (actinic) elastosis)
Spongiotic (eczematous or contact) dermatitisAg contacts epidermisLangerhans
cell/CD4+ T cell mediatededema into epidermis, spongiosis +/- vesicles
Erythema multiformehypersensitivity reaction to medication, herpes simplex virus,
mycoplasma, collagen vascular diseases, lymphomas, carcinoma
Erythema multiforme, skin involvement onlyHSV (usually)
Erythema multiforme, skin and mucous membranes, feverSteven Johnson Syndrome
(usually due to drugs)
Erythema multiforme, total skin sloughage like a burn patientToxic epidermal
necrolysis (TEN) (usually due to drugs)
Lichen planusthought to be delayed hypersensitivity reaction resulting in damage to
basal keratinocytes, acanthosis, hypergranulosis, and hyperkeratosis, vacuolar basal layer
damage (hydropic degeneration), eosinophilic necrosis of keratinocytes, band-like
lymphocytic infiltrate*, Koebner phenomenon*, thick purplish lesions
Systemic LEskin and other organs
Subacute LEskin +/- other organs
Discoid LElocalized to skin
Lulpus Erythematosusautoimmune rxn to basal keratinocytes (+/- organs) hydropic
degeneration and eosinophilic necrosis
On IGF: granular IgG and C3 along DE junctionLE
In DLE: IF positive in lesional skin only
In SCLE, SLE: IF positive in lesional and non-lesional skin
Keratinocytes proliferate at twice the normal rate, resulting in acanthosis with elongated
rete ridges and dermal papilla (look like test tubes)psoriasis vulgaris
PMNs migrate into epidermis and stratum corneumMunro’s microabscessespsoriasis
vulgaris
White scales and Koebner phenomenonpsoriasis vulgaris
IgG binds to intercellular desmoglein 3 (cadherin)intercellular IgG between spinous
keratinocytesacantholysis (loss of intercellular connection)suprabasilar
vesiclePemphigus vulgaris (potentially fatal due to infection)
*Nikolsky sign (pressure on edge of blister causes blister to expand)Pemphigus
vulgaris
IgG+C3 bind to hemidesmosomes at DE junctionsubepidermal blisterlinear IgG and
C3 along DE junction on IFBullous pemphigoid (usually self-limited, middle aged to
elderly, at sites of friction)tensa bulla (subepidermal) filled with clear fluid, heal w/o
scarring
IgA to anchoring fibrils in BMgranular IgA at tips of dermal papillasubepidermal
bulla at tips of dermal papillaDermatitis herpetiformis (pruritic vesicles with red
base)Celiac Disease association and HLA B8
SclerodermaCD4+ T cells release cytokines and cause collagen formation and fibrosis,
CD8+ T cells damage endothelium by granzyme A leading to periadventitial
fibrosisAnti-Scl70 (DNA topoisomerase; specific), anti-centromere ab (more common
in limited scleroderma)CREST syndrome (calcinosis, Raynaud phenomenon, esophageal
dysmotility, sclerodactyly, and telangiectasia)
Erythema nodosumidiopathic, early there are PMNs and edema, late there are giant
cells and fibrosispainful, indurated subcutaneous nodules over anterior lower legs3040 yo females, usually self-limitedassociated with Strep throat, inflammatory bowel
disease, TB, fungi, drugs, sarcoidosis, malignancy
Hypersensitivity vasculitis, Type II hypersensitivity reaction (immune complexes deposit
in vessel walls), leukocytoclastic vasculitisdrugs, infection, collagen vascular diseases
(SLE, RA, Pernicious Anemia, Wegener’s)
Palpable purpuraHenoch Schoenlein (immune complex vasculitis)triad of purpura,
arthritis (ankles, knees, elbows), and abdominal pain; 40% have kidney involvement
(minor loss of protein and blood)
Acral melanomaunder nails, palms, solesvery aggressive
Breslow thickness (depth of invasion in mm)melanomamost important prognostic
indicator
Clark levelhistologic level of invasion
Moh’s procedure (frozen sections until clear margins)Basal cell carcinoma
Sezary SyndromeT cell leukemia with T cell lymphoma of the skin
Mycosis fungoidesT cell lymphoma skin
Pautrier abscessMycosis fungoides
Proliferation and death of infected keratinocytesmolluscum contagiosum
Umbilicated lesions (center is deeper than surrounding, depressed in center)molluscum
contagiosum
Lymphocytes with cerebriform (convoluted) nucleiSezary Syndrome
Dermatomal rashshingles
Abnormal elastic fiberssenile or actinic
Rodent ulcer (erodes surrounding tissue)basal cell carcinoma
HHV8Kaposi Sarcoma
Subcorneal lesions (right under keratin) and honey-colored crustimpetigo (strep
infection)
Scabies (left out of handout and told to add)
-Scabere= latin for “to scab”
-Mitesarcoptes scabeibury into skinallergic itching
-close contact transmission
-linear streaks (forms tunnels in skin)
-responds to landin lotion
Human papilloma virus (usually types 2 and 4)incorporated in host
DNApapulespapillomatous on microscopyverruca vulgaris (common wart on
hands, arms, etc.) NO risk of malignant transformation (vacuoles—koilocytes—
cytopathic effect)
condyloma acuminatum (genital wart)HPV types 6,11 (low risk types) sometimes
16,18 (high risk types)verrucous papulesubtle cytopathic effect
Infected keratinocytes undergo cell deathHerpes Virus family (Herpes Simplex Virus,
Varicella Zoster, Herpes-Zoster)
Cold soreHSV 1
HSV 2genital infection (painful, erythematous clustered vesicles)
Dewdrops on a rose petal vesiclesVaricella Zoster
Stress, immunosuppression, illness + prior infection with VZVdermatomal
rashshingles
Member of pox viridae that causes both proliferation and destruction (death) of
keratinocytesMolluscum Contagiosum
Pink, grouped papules with central umbilicationMolluscum Contagiosum
Vesicles/erosions with honey-colored crust, subcorneal lesionsimpetigostaph aureus
and group A streptococcus
Trichophyton and Microsporumringworm
Benign, exophytic, greasy verrucous papule/plaque with keratin plugsSeborrheic
keratosis (may be mistaken for melanoma)
Scaly, erythematous papules/plaques arising on sun-exposed areas with a sandpaper
texture (due to a lot of keratin)premalignant lesion called actinic keratosis
Squamous cell carcinoma in situ (Bowen’s Disease)full thickness dysplasia of
keratinocytes in sun-exposed areas, especially lips, mucosal surfaces, genitalialarger
erythematous, scaly plaques
Cup-shaped invagination of squamous epithelium with keratin-filled center, which
enlarges rapidly and can regress; may be a squamous cell carcinomakeratoacanthoma
Basaloid keratinocyte nodular or nested growth (and pallisading), most common nonmelanoma skin cancer, called rodent ulcer because erodes surrounding skin, rarely
metastasizesbasal cell carcinoma
Moh’s surgeryused for Basal cell carcinoma: keep doing frozen sections until clear
margins
Keratin pearls and invasive skin cancer, keratotic nodule with dermal induration,
erythematous, irregular bordersSquamous cell carcinoma
Tumor like growth of granulation tissue in pregnant woman, red papule with or w/o
ulcerationPyogenic granuloma
Kaposi’s sarcoma two types: acral sites (classic) in elderly (lower limbs due to venous
stasis) or widespread HIV-associated hemorrhagic patches or plaques due to HHV-8
virus
Growth of spindled peripheral nerve fibers in fascicles (whorls), café-au-lait spots,
associated with MEN2b syndromeNeurofibroma (benign)
Von Recklinghausen’s syndrome= malignant transformation of of neurofibroma
T-cell lymphoma (aka mycosis fungoides)= most common presentation of NonHodgkin’s lymphoma of the skin=itchy, red, scaly raised plugs (may be mistaken for
eczema)
Sezary Syndrome= T-cell lymphoma of a large amount of skin + leukemic phase (more
serious than just skin)
Pautrier microabscess= small aggregate of malignant lymphocytes in skinT-cell
lymphoma (Mycosis fungoides)
Lymphocytes with cerebriform nuclei on peripheral blood smearSezary Syndrome
Increased melanocytes in linear pattern along basal layerlentigodark brown macule
Nests of melanocytes at DE junction, at tips of rete ridgesjunctional nevusdark
brown macule
Compound nevusnests of melanocytes in both epidermis and dermisdark brown to
tan papule
Intradermal nevusnests of melanocytes in the dermistan to flesh-colored papule
ABCD of premalignant tumors:
Asymmetry
Border Irregularity
Color variability
Diameter > or = 6mm
Dysplastic nevusatypical nevusClark’s nevus *familial type results in hundreds of
lesions with high risk for melanomajunctional or compound melanocyte distribution
Risk factors for malignant melanoma in situ= fair complexion, severe childhood
sunburns, history of dysplastic nevi, history of melanoma in primary relative
Atypical melanocytes proliferating within the epidermismalignant melanoma in situ
(appears a little darker than dysplastic nevi and looks nodular)
Lentigo maligna melanomaface of elderly
Superficial spreading melanomasun-exposed areas, radial growth, then vertical growth
Nodular melanomamore aggressive melanoma and invades deep
Acral lentiginous melanomaacral sites, often deep at time of dx, non-sun-exposed areas
such as fingers, palms, soles, under nailsaggressive
Acanthosis Nigricans (black discoloration in axilla, neck, groin)Type I (rapidly
progressing sudden onset on face, palms, trunk) GI malignancy, Type II (not
associated with malignancy, family auto dominant), Type III (most common, slow
onset)obesity, type II diabetes (check fasting blood sugar and will be high)
Erythema chronicum migransLyme Disease
Necrobiosis Lipoidica= yellow plaques, atrophic centers, on shinsDiabetes Mellitus
Eruptive Xanthomas= yellow papules on extensor surfacesDiabetes Mellituscheck
fasting blood sugar and serum triglycerides
Granuloma Annulare= annular plaque on dorsal hands or feetDiabetes Mellituscheck
fasting blood sugar and KOH (to rule out tinea)
Xanthelasma= yellow plaques on eyelidsHyperlipidemia (order lipid profile)
Psoriasis=well demarcated erythematous plaques with silver scales on elbows, knees,
buttocksHyperlipidemia (check lipid profile, CAD risk factors)
Systemic LupusErythematous plaques, bilateral cheeksANA, Anti-ro/la, AntidsDNA, Anti-smooth muscle
Pagets Diseaseerythematous patch/plaque breastmammogram, ultrasound, MRI
Erythema Nodosum= tender nodules, erythematous nodules on anterior shinsdo strep
culture/ASO, CXR (Sarcoidosis), Stool cultures, Colonoscopy (Crohn’s/UC), Medication
History (OCP)
Chronic Urticaria do CBC (increased WBC, viral), ANA (lupus), TSH, CXR
(lymphoma), UA